NM_002435.3(MPI):c.820dup (p.Val274fs) AND MPI-congenital disorder of glycosylation

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 28, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001944655.4

Allele description [Variation Report for NM_002435.3(MPI):c.820dup (p.Val274fs)]

NM_002435.3(MPI):c.820dup (p.Val274fs)

Gene:

MPI:mannose phosphate isomerase [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

15q24.1

Genomic location:

Preferred name:

NM_002435.3(MPI):c.820dup (p.Val274fs)

HGVS:

NC_000015.10:g.74896301dup
NG_008921.1:g.11233dup
NM_001289155.2:c.820dup
NM_001289156.2:c.670dup
NM_001289157.2:c.637dup
NM_001330372.2:c.760dup
NM_002435.3:c.820dupMANE SELECT
NP_001276084.1:p.Val274fs
NP_001276085.1:p.Val224fs
NP_001276086.1:p.Val213fs
NP_001317301.1:p.Val254fs
NP_002426.1:p.Val274fs
NC_000015.9:g.75188641_75188642insG
NC_000015.9:g.75188642dup

Protein change:

V213fs

Links:

dbSNP: rs1567268668

NCBI 1000 Genomes Browser:

rs1567268668

Molecular consequence:

NM_001289155.2:c.820dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001289156.2:c.670dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001289157.2:c.637dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001330372.2:c.760dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_002435.3:c.820dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: MPI-congenital disorder of glycosylation
Synonyms:: CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ib; CDG Ib; Congenital disorder of glycosylation type 1B; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011257; MedGen: C1865145; Orphanet: 79319; OMIM: 602579

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002129265	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 28, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19862844, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002129265

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 28, 2021)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Congenital disorders of glycosylation: an update on defects affecting the biosynthesis of dolichol-linked oligosaccharides.

Haeuptle MA, Hennet T.

Hum Mutat. 2009 Dec;30(12):1628-41. doi: 10.1002/humu.21126. Review.

PubMed [citation]

PMID:: 19862844

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002129265.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant has not been reported in the literature in individuals affected with MPI-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Val274Glyfs*31) in the MPI gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MPI are known to be pathogenic (PMID: 19862844).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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